The COL6A1 rs201153092 single nucleotide polymorphism, associates with thoracic ossification of the posterior longitudinal ligament

Abstract

Thoracic ossification of the posterior longitudinal ligament (T-OPLL) is one of the most common factors that causes thoracic spinal stenosis, resulting in intractable myelopathy and radiculopathy. Our previous study reported that the rs201153092 polymorphism present in the collagen 6A1 (COL6A1) gene was a potentially pathogenic locus for the development of T-OPLL. The present study aimed to determine whether the rs201153092 mutation causes abnormal expression of COL6A1 in Han Chinese patients with T-OPLL, and to examine the effects of this mutation on osteogenesis by establishing a model of osteogenic differentiation. COL6A1 gene mutant and wild-type mouse 3T3-E1 embryonic osteoblast models were constructed to induce the differentiation of these cells into osteoblasts. The potential of the mutation site to induce abnormal expression of the COL6A1 gene and osteogenic markers was assessed via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that the rs201153092A mutation site resulted in significantly increased COL6A1 gene expression levels in the OPLL tissues obtained following clinical surgery. This mutation was shown to play an important role in the development of T-OPLL by regulating the overexpression of the COL6A1 gene and significantly increasing the expression levels of osteogenic markers. The findings of the present study suggested that the rs201153092A mutant variant could increase the expression levels of COL6A1 and consequently play a role in the pathogenesis of T-OPLL.

Proteomic Profiling of the Human Fetal Multipotent Mesenchymal Stromal Cells Secretome

“…Classic osteogenic factors observed in the hMSCs secretomes were also absent in FetMSCs secretome. Nevertheless, we observed some other proteins involved in osteogenic differentiation: COL6A1 [32], MMP2 [33], tenascin [34], semaphorin-7A [35], stanniocalcin-1 [36], exostosin-1 and Exostosin-2 [37]. On the other hand, inhibitors of osteogenic differentiation were also observed: gremlin-1 [38], insulin-like growth factor binding protein-3 [39] and twisted gastrulation protein homolog 1 [40].…”

Degenerative Thoracic Myelopathy: A Scoping Review of Epidemiology, Genetics, and Pathogenesis

“…Increased expression of IL17RC and COL6A1, two osteogenic genes, have been associated with OPLL. [84][85][86][87] IGF-1 has been associated with ligament ossification, 88 which may explain the association between acromegaly and OPLL. 89 Hyperleptinemia and hyperinsulinemia are other factors involved in the development of OPLL, 90 as is obesity.…”